JAMA: 出院后使用托拉塞米与呋塞米对心衰患者全因病死率的影响

Key Points

Question  Does torsemide reduce all-cause mortality compared with furosemide in patients with heart failure following hospitalization? 与住院后心力衰竭患者的速尿相比，托拉塞米是否能降低全因死亡率？

Findings  In this randomized clinical trial of 2859 patients, 26.1% of patients randomized to torsemide and 26.2% randomized to furosemide died over a median follow-up of 17.4 months without a significant difference between groups. 在这项包含 2859 名患者的随机临床试验中，26.1% 随机分配至托拉塞米组的患者和 26.2% 随机分配至呋塞米组的患者在 17.4 个月的中位随访期间死亡，两组间无显着差异。

Meaning  Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months; however, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. 在因心力衰竭住院后出院的患者中，与呋塞米相比，托拉塞米并未导致 12 个月内全因死亡率的显着差异； 然而，对这些发现的解释受到失访、参与者交叉和不依从的限制。

Abstract

Importance  Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. 尽管呋塞米是心力衰竭患者最常用的袢利尿剂，但一些研究表明托拉塞米具有潜在益处。

Objective  To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. 确定在因心力衰竭住院的患者中，与呋塞米相比，托拉塞米是否能降低死亡率。

Design, Setting, and Participants  TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. TRANSFORM-HF 是一项开放标签、实用的随机试验，招募了在美国 60 家医院因心力衰竭（无论射血分数如何）住院的 2859 名参与者。 招募时间为 2018 年 6 月至 2022 年 3 月，死亡随访 30 个月，住院随访 12 个月。 后续数据收集的最后日期是 2022 年 7 月。

Interventions  Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage.托拉塞米 (n = 1431) 或呋塞米 (n = 1428) 的环利尿策略采用研究者选择的剂量。

Main Outcomes and Measures  The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. 主要结果是事件发生时间分析中的全因死亡率。 有 5 个次要结果，其中全因死亡率或全因住院率和评估超过 12 个月的总住院率在等级中最高。 预设的主要假设是，与呋塞米相比，托拉塞米可将全因死亡率降低 20%。

Results  TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. TRANSFORM-HF 随机分配了 2859 名中位年龄为 65 岁（IQR，56-75）的参与者，其中 36.9% 为女性，33.9% 为黑人。 在中位随访 17.4 个月期间，共有 113 名患者（托拉塞米组 53 名 [3.7%] 和速尿组 60 名 [4.2%]）在试验完成前撤回同意。 托拉塞米组 1431 例患者中有 373 例 (26.1%) 死亡，速尿组 1428 例患者中有 374 例 (26.2%) 死亡（风险比，1.02 [95% CI，0.89-1.18]）。 随机分组后超过 12 个月，托拉塞米组 677 名患者 (47.3%) 和速尿组 704 名患者 (49.3%) 发生全因死亡或全因住院（风险比，0.92 [95% CI，0.83- 1.02])。 托拉塞米组 536 名参与者和速尿组 577 名参与者共计 940 人住院（率比，0.94 [95% CI，0.84-1.07]）。 结果在预先指定的亚组中相似，包括射血分数降低、轻度降低或保留的患者。

Conclusions and Relevance  Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. 在因心力衰竭住院后出院的患者中，与呋塞米相比，托拉塞米并未导致 12 个月内全因死亡率的显着差异。 然而，对这些发现的解释受到失访、参与者交叉和不依从的限制。

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03296813